Abstract

Background

Cell lines are used in experimental investigation of cancer but their capacity to
represent tumor cells has yet to be quantified. The aim of the study was to identify
significant alterations in pathway usage in cell lines in comparison with normal and
tumor tissue.

Methods

This study utilized a pathway-specific enrichment analysis of publicly accessible
microarray data and quantified the gene expression differences between cell lines,
tumor, and normal tissue cells for six different tissue types. KEGG pathways that
are significantly different between cell lines and tumors, cell lines and normal tissues
and tumor and normal tissue were identified through enrichment tests on gene lists
obtained using Significance Analysis of Microarrays (SAM).

Results

Cellular pathways that were significantly upregulated in cell lines compared to tumor
cells and normal cells of the same tissue type included ATP synthesis, cell communication,
cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism,
and proteasome. Results on metabolic pathways suggested an increase in the velocity
nucleotide metabolism and RNA production. Pathways that were downregulated in cell
lines compared to tumor and normal tissue included cell communication, cell adhesion
molecules (CAMs), and ECM-receptor interaction. Only a fraction of the significantly
altered genes in tumor-to-normal comparison had similar expressions in cancer cell
lines and tumor cells. These genes were tissue-specific and were distributed sparsely
among multiple pathways.

Conclusion

Significantly altered genes in tumors compared to normal tissue were largely tissue
specific. Among these genes downregulation was a major trend. In contrast, cell lines
contained large sets of significantly upregulated genes that were common to multiple
tissue types. Pathway upregulation in cell lines was most pronounced over metabolic
pathways including cell nucleotide metabolism and oxidative phosphorylation. Signaling
pathways involved in adhesion and communication of cultured cancer cells were downregulated.
The three way pathways comparison presented in this study brings light into the differences
in the use of cellular pathways by tumor cells and cancer cell lines.